Wave Life Sciences Ltd (NASDAQ:WVE) announced results from its Phase 1b/2a SELECT-HD trial of WVE-003, which is being developed as a potential disease-modifying therapeutic for Huntington's disease (HD).
WVE-003 is designed to lower mutant huntingtin (mHTT) protein and preserve healthy, wild-type huntingtin (wtHTT) protein.
In the multidose portion of the SELECT-HD study (n=23), participants received either every-eight-week (Q8W) intrathecal doses of 30 mg WVE-003 (n=16) or placebo (n=7), with 12 weeks of follow-up.
Key results are as follows:
- WVE-003 was generally safe and well-tolerated, with no Serious Adverse Events (SAEs) reported; ventricular volume was in line with natural history.
- Significant mHTT protein lowering was observed throughout the 28-week assessment period.
- At 24 weeks (8 weeks after the last dose), mean mHTT lowering in cerebrospinal fluid (CSF) was 46% versus placebo (p=0.0007).
- At 28 weeks (12 weeks after the last dose), mean mHTT lowering in CSF was 44% versus placebo (p=0.0002), which supports quarterly or less frequent dosing.
- wtHTT protein was preserved throughout the 28-week assessment period, validating allele-selective silencing. Additionally, statistically significant increases were observed in wtHTT protein versus placebo.
- wtHTT protein supports the health and function of neurons and is crucial for CSF flow in the ventricles.
- mHTT also has a detrimental effect on wtHTT at the protein level, further decreasing its function. Only selective lowering of mHTT can potentially relieve its negative impact on wtHTT protein function.
- Most WVE-003-treated participants had neurofilament light protein (NfL) levels that were in the range of placebo or had NfL levels that increased and returned to the range of placebo.
- At 24 weeks (the last MRI assessment), mHTT reduction was correlated with slowing of caudate atrophy (R=-0.50; p=0.047). Caudate atrophy is an imaging biomarker predictive of clinical outcomes, including clinically meaningful worsening of Total Motor Score (TMS).
- A slowing of decline was observed for TMS for WVE-003 versus placebo (4.25 mean difference at 24 weeks, p=not significant).
Wave expects that its current cash and cash equivalents of $181 million will be sufficient to fund operations into the fourth quarter of 2025.
Price Action: WVE shares traded down 3.07% at $5.05 at last check Tuesday.
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